Prosthetic Metals: Release, Metabolism and Toxicity.

The development of metallic joint prostheses has been ongoing for more than a century alongside advancements in hip and knee arthroplasty. Among the materials utilized, the Cobalt-Chromium-Molybdenum (Co-Cr-Mo) and Titanium-Aluminum-Vanadium (Ti-Al-V) alloys are predominant in joint prosthesis construction, predominantly due to their commendable biocompatibility, mechanical strength, and corrosion resistance. Nonetheless, over time, the physical wear, electrochemical corrosion, and inflammation induced by these alloys that occur post-implantation can cause the release of various metallic components. The released metals can then flow and metabolize in vivo, subsequently causing potential local or systemic harm. This review first details joint prosthesis development and acknowledges the release of prosthetic metals. Second, we outline the metallic concentration, biodistribution, and elimination pathways of the released prosthetic metals. Lastly, we discuss the possible organ, cellular, critical biomolecules, and significant signaling pathway toxicities and adverse effects that arise from exposure to these metals.

Compositional effects on structural, electronic, elastic, piezoelectric and dielectric properties of GaInN alloys: a first-principles study.

We conduct a comprehensive theoretical analysis of wurtzite GaxIn1-xN ternary alloys, focusing on their structural, electronic, elastic, piezoelectric, and dielectric properties through rigorous first-principles calculations. Our investigation systematically explores the influence of varying Ga composition (x = 0%, 25%, 50%, 75%, 100%) on the alloy properties. Remarkably, we observe a distinctive non-linear correlation between the band gap and Ga concentration, attributable to unique slopes in the absolute positions of the valence band maximum and conduction band minimum with respect to Ga concentration. Our effective band structure analysis reveals the meticulous preservation of Bloch characters near band extrema, minimizing charge carrier scattering. Furthermore, we scrutinize deviations from linear Vegard-like dependence in elastic, piezoelectric, and dielectric constants. Additionally, our calculations encompass various optical properties, including absorption coefficient, reflectivity, refractive index, energy loss function, and extinction coefficient. We analyze their trends with photon energy, providing valuable insights into the optical behavior of GaxIn1-xN alloys. Our results, in excellent agreement with available experimental data, significantly contribute to a deeper understanding of the alloys' electronic properties. This study offers valuable insights that may illuminate potential applications of GaxIn1-xN alloys in diverse technological fields.

Prognostic analysis and treatment utilization of different treatment strategies in elderly esophageal cancer patients with distant metastases: a SEER database analysis.

PURPOSE: The purpose of this study was to explore which therapeutic strategy is more beneficial for elderly esophageal cancer (EC) patients with distant metastasis, the treatment utilization status and the screening of factors related to prognosis, so as to better guide the treatment of these patients. METHODS: Patients in the Surveillance Epidemiology and End Results (SEER) database were divided into chemoradiotherapy (Group A), chemotherapy (Group B), radiotherapy (Group C), and no treatment (Group D) according to different treatment methods. Propensity score matching (PSM) was performed to adjust for baseline differences between the two groups. Overall survival (OS) and esophageal cancer-specific survival (ECSS) was calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: A total of 7027 patients were included in this study, 5739 males (81.7%) and 1288 females (18.3%) with the median age was 70 (60-98). In the original cohort, the number of patients in the four groups was 2260 (Group A), 2087 (Group B), 945 (Group C) and 1735 (Group D), respectively. After PSM, there was no significant difference in mean OS (A vs B, 13.5 months VS 13.4 months, P = 0.511) and mean ECSS (A vs B, 15.6 vs 15.5 months, P = 0.374), while both OS (B vs C, 7 vs 3 months, P < 0.001) and ECSS (B vs C, 8 vs 3 months, P < 0.001) of chemotherapy alone were significantly better than those of radiotherapy alone. Subgroup analysis of patients older than 80 years showed that the median OS (A vs B, 7 vs 6 months) and median ECSS (A vs B, 8 vs 7 months) of Group A were significantly better than those of Group B (P < 0.05). In addition, all patients were randomly divided into a training set and a validation set with a ratio of 7:3. Based on the independent risk factors for OS, a nomogram model was constructed and validated. CONCLUSION: For elderly EC patients with distant metastasis, aggressive treatment was still necessary after a comprehensive assessment of the patient's physical condition, especially for patients over 80 years old, and chemoradiotherapy maybe still the first choice. In addition, a nomogram model was constructed to intuitively and accurately evaluate the prognosis of this population.

Comparison of the Therapeutic Effects of Iodine-125 Seed Implantation and Conventional Radiochemotherapy for Advanced Esophageal Cancer.

BACKGROUND: The purpose of this study was to explore the feasibility, safety and efficacy of iodine-125 seed implantation in the treatment of dysphagia of advanced esophageal cancer. METHODS: We retrospectively analyzed patients with advanced esophageal cancer who underwent EUS-guided iodine-125 seed implantation or conventional chemoradiotherapy in our hospital. The propensity score match was used to reduce the baseline differences. RESULTS: A total of 127 patients were enrolled, 17 patients received EUS-guided iodine 125 seed implantation (Group A), 31 patients received radiotherapy (Group B), 38 patients received chemotherapy (Group C) and 41 patients received chemotherapy combined with radiotherapy (Group D). At half month postoperatively, the dysphagia remission rate in Group A (100%) was better than that in Groups B (39.3%), C (20%), D (15.8%), respectively, in the original cohort (P < 0.01); At 1 month postoperatively, the dysphagia remission rate in Group A (86.7%) was better than that in Group B (57.1%) (P > 0.05), Group C (25.7%) (P < 0.05) and Group D (34.2%) (P < 0.05), respectively, in the original cohort. There was no statistically significant difference in median overall survival (OS) between Group A (16 months) and Group B (37 months) (P = 0.149), and between Group A (16months) and Group C (16 months) (P = 0.918) in the original cohort. The mean OS of Group D (54 months) was better than that of Group A (20 months) in the original cohort (P = 0.031). The incidences of grade ≥2 myelosuppression in Groups B, C, and D were 12.9%, 28.9%, and 43.9%, respectively; the incidence of grade ≥2 gastrointestinal adverse events in Groups B, C, and D were 12.9%, 15.8%, 12.2%, respectively. No serious adverse events were found in Group A. The radiation dose around the patient was reduced to a safe range after the distance from the implantation site was more than 1 m (4.2 ± 2.6 µSv/h) or with lead clothing (0.1 ± 0.07 µSv/h). CONCLUSIONS: Compared with conventional radiotherapy or chemotherapy alone, iodine-125 seed implantation might improve dysphagia more quickly and safely, further clinical data is needed to verify whether it could effectively prolong the OS of patients.

Complications of primary total hip arthroplasty among patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and primary osteoarthritis.

BACKGROUND: Limited information exists comparing the perioperative complications of the different inflammatory arthropathies (IAs) after total hip arthroplasty (THA). Our study was aimed to (1) compare perioperative complications and (2) determine the most common complications between the different IA subtypes compared with patients with primary osteoarthritis (OA) undergoing primary THA and (3) find whether the difference in postoperative complications also exists between different IA after THA. METHODS: The Nationwide Inpatient Sample (NIS) was used to identify patients with Rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis (AS), and primary OA undergoing unilateral THA between 2005 and 2014. Preoperative diagnosis, comorbidities, and postoperative complications were determined using the International Classification of Disease Clinical Modification version 9 codes. The prevalence of perioperative complications was compared between patients with IA and primary OA and between patients with different IA. RESULTS: When compared with patients with primary OA, patients with RA had significantly more postoperative surgical and medical complications. Yet there are just several medical complications differences exist between PA and primary OA or AS and primary OA, including stroke and acute renal failure for psoriatic arthritis and urinary tract infection and pneumonia for AS. What is more, there were also several differences in perioperative medical complications seen in patients with different IA. CONCLUSION: Except for patients with RA, the differences in perioperative complications was small between patients with IA and primary OA and between patients with different types of IA.

Systematic Review and Meta-Analysis of the Evaluation of the Efficacy of Manipulation and Cervical Traction in the Treatment of Radical Cervical Spondylosis.

Background: With the accelerated pace of life in modern society, changes in work style, and the popularity of computers, the prevalence of cervical spondylosis (CSR) is increasing, and the age of onset is advancing. Once suffering from this disease, it is often difficult to cure and recurring, with complex clinical symptoms, causing a serious impact on human health. Objective: To evaluate the efficacy of manipulation and cervical traction in the treatment of radical cervical spondylosis. Methods: The PubMed, CNKI, and Wanfang databases were searched for literature. The literature related to this study was included according to selective criteria and inhibitory elimination criteria, and valuable information was selected for statistical analysis, resulting in a total of 11 randomized controlled trials with 994 subjects. Results: The short-term efficacy of manual treatment for CSR was superior to that of cervical traction alone (P < 0.05); subgroup analysis showed that the short-term efficacy of pulling or rotational manipulation was superior to that of cervical traction (P < 0.05). The mean difference between symptoms and manipulation VAS scores was higher before and after treatment when compared with cervical traction for CSR (P < 0.05); the subgroup analysis showed that VAS scores, upper extremity anesthesia scores, and survivorship scores were lower for pulling or rotating manipulation than for cervical traction (P < 0.05). Conclusion: The advantages of manual therapy in terms of short-term efficacy, VAS pain scores, neck pain, upper extremity anesthesia, and survivorship improvement provide a theoretical basis for its clinical impact.

Using a degradable three-layer sandwich-type coating to prevent titanium implant infection with the combined efficient bactericidal ability and fast immune remodeling property.

Titanium (Ti) implant-associated infections are a challenge in orthopedic surgery, for which a series of antibacterial coatings have been designed and fabricated to reduce the risk of bacterial contamination. Herein, we created a degradable three-layer sandwich-type coating to achieve long-term antibacterial effects while simultaneously reconstructing the local immune microenvironment. The vancomycin (Van)-loaded vaterite coating constitutes the outer and inner layers, whereas Interleukin-12 (IL-12)-containing liposomes embedded in sodium alginate constitutes the middle layer. Van, released from the vaterite, demonstrated a favorable and rapid bactericidal ability against the representative methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains. The released IL-12 exhibited the desired immune reconstitution abilities, actively facilitating defenses against subsequent bacterial invasions. Furthermore, the biocompatibility and cell-binding feature of the multifunctional coating was beneficial for achieving solid interface intergradation. Overall, the benefits of the three-layer sandwich-type coating, including the convenient fabrication process, efficient antimicrobial activity, fast immune remodeling property, fine cell-binding feature, and biodegradability, highlight its promising translational potential in preventing implant infection. STATEMENT OF SIGNIFICANCE: To prevent titanium implant infections, researchers have designed various antibacterial coatings. However, most of these coatings focused only on killing the invading bacteria over a limited postoperative period. However, the local immune microenvironment is compromised during surgery. Local immune deflection impedes the ability of the local immune defenses to clear bacteria and limits immune memory building from active defense against long-term subsequent bacterial invasions. Furthermore, these coatings are usually nondegradable and differ substantially from bone components, thereby impairing the integration of the coating and bone interface and generating concerns about implant stability and bacterial contamination. In this work, we synthesized a degradable coating that provides sustained antibacterial activity, promotes immune reconstitution, and simultaneously achieves solid bone integration.

Effect of Remote Ischemic Conditioning vs Usual Care on Neurologic Function in Patients With Acute Moderate Ischemic Stroke: The RICAMIS Randomized Clinical Trial.

Importance: Preclinical and clinical studies have suggested a neuroprotective effect of remote ischemic conditioning (RIC), which involves repeated occlusion/release cycles on bilateral upper limb arteries; however, robust evidence in patients with ischemic stroke is lacking. Objective: To assess the efficacy of RIC for acute moderate ischemic stroke. Design, Setting, and Participants: This multicenter, open-label, blinded-end point, randomized clinical trial including 1893 patients with acute moderate ischemic stroke was conducted at 55 hospitals in China from December 26, 2018, through January 19, 2021, and the date of final follow-up was April 19, 2021. Interventions: Eligible patients were randomly assigned within 48 hours after symptom onset to receive treatment with RIC (using a pneumatic electronic device and consisting of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg) for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971). Main Outcomes and Measures: The primary end point was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 1893 eligible patients with acute moderate ischemic stroke who were randomized (mean [SD] age, 65 [10.3] years; 606 women [34.1%]), 1776 (93.8%) completed the trial. The number with excellent functional outcome at 90 days was 582 (67.4%) in the RIC group and 566 (62.0%) in the control group (risk difference, 5.4% [95% CI, 1.0%-9.9%]; odds ratio, 1.27 [95% CI, 1.05-1.54]; P = .02). The proportion of patients with any adverse events was 6.8% (59/863) in the RIC group and 5.6% (51/913) in the control group. Conclusions and Relevance: Among adults with acute moderate ischemic stroke, treatment with remote ischemic conditioning compared with usual care significantly increased the likelihood of excellent neurologic function at 90 days. However, these findings require replication in another trial before concluding efficacy for this intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT03740971.

Perfectionistic Concerns and Mobile Phone Addiction of Chinese College Students: The Moderated Mediation of Academic Procrastination and Causality Orientations.

This study aimed to investigate the effect of perfectionistic concerns (PC) on mobile phone addiction (MPA) and the mediating role of academic procrastination (AP), as well as the moderating role of causality orientations (autonomous/controlled/impersonal orientation). A cross-sectional sample of 625 Chinese college students (20.8% male, mean age = 20.47 years old) completed measures of PC, AP, causality orientations, and MPA. We analyzed the survey data using structural equation modeling (SEM) in Mplus 8.0. PC was positively related to MPA. In addition, AP partially mediated this association. The hypothesized moderating effect of autonomous orientation and controlled orientation was not supported. Impersonal orientation moderated the second stage of the mediating effect of AP on the PC-MPA link in that the mediating effect was positive when impersonal orientation was high, while the mediating effect was not significant when impersonal orientation was low. The findings confirm the importance of investigating how individual difference (i.e., PC) contributes to MPA. The implications of the findings for relieving MPA or preventing college students from developing MPA are also discussed deeply and thoroughly.

Influence of frailty and its interaction with comorbidity on outcomes among total joint replacement.

BACKGROUND: Patients with frailty get more and more attention in clinical practice. Yet, no large-scale studies have explored the impact of frailty on the perioperative acute medical and surgical complications following TJA. what is more, comorbid diseases may lead, at least additively, to the development of frailty. There also no studies to find the possible interaction between comorbidity and frailty on the postoperative complications after TJA. METHODS: Discharge data of 2,029,843 patients who underwent TJA from 2005 to 2014 from the National Inpatient Sample (NIS) database, which was analyzed using cross-tabulations and multivariate regression modeling. Frailty was defined based on frailty-defining diagnosis clusters from frailty-defining diagnosis indicator of Johns Hopkins Adjusted Clinical Groups. RESULTS: Among patients who underwent total joint replacement surgeries, 50,385 (2.5%) were identified as frail. Frailty is highly associated with old age, especially for those over the age of 80, meanwhile females and black races have a high Charlson comorbidity index (CCI) of ≥ 3, together with emergency/urgent admission and teaching hospital. While comorbidity is associated with greater odds of acute medical complications, and frailty has a better predictive effect on in-hospital deaths, acute surgical complications. Furthermore, frailty did not show an enhancement in the predictive power of the Charlson comorbidity score for postoperative complications or in-hospital deaths but postoperative LOS and hospitalization costs. CONCLUSION: Frailty can be used to independently predicted postoperative surgical and medical complications, which also has a synergistic interaction with comorbidity for patients who are preparing to undergo TJA.

Innovative ochre processing and tool use in China 40,000 years ago.

Homo sapiens was present in northern Asia by around 40,000 years ago, having replaced archaic populations across Eurasia after episodes of earlier population expansions and interbreeding1-4. Cultural adaptations of the last Neanderthals, the Denisovans and the incoming populations of H. sapiens into Asia remain unknown1,5-7. Here we describe Xiamabei, a well-preserved, approximately 40,000-year-old archaeological site in northern China, which includes the earliest known ochre-processing feature in east Asia, a distinctive miniaturized lithic assemblage with bladelet-like tools bearing traces of hafting, and a bone tool. The cultural assembly of traits at Xiamabei is unique for Eastern Asia and does not correspond with those found at other archaeological site assemblages inhabited by archaic populations or those generally associated with the expansion of H. sapiens, such as the Initial Upper Palaeolithic8-10. The record of northern Asia supports a process of technological innovations and cultural diversification emerging in a period of hominin hybridization and admixture2,3,6,11.

Chitin/corn stalk pith sponge stimulated hemostasis with erythrocyte absorption, platelet activation, and Ca2+-binding capabilities.

Chitin (CT) is widely used as a hemostatic material in surgical sponges, although its efficacy needs improvement to promote the clotting process. In this study, another green biomass, corn stalk pith (CSP), was incorporated into CT through ball milling to fabricate CT-CSP composite hemostatic sponges to enhance erythrocyte absorption, platelet activation, and clotting factor accumulation (Ca2+). In vitro hemostatic analysis indicated that CSP incorporation greatly promoted the coagulation process, with a much lower blood clot index and higher blood clot stability. In addition, the composite sponge promoted more platelet adhesion and activation, and the composite sponge demonstrated a greater ability to bind clotting factors (Ca2+). Consistently, it achieved complete hemostasis with less blood loss and a shorter hemostatic time in a rat liver injury-model. This composite hemostatic sponge is sustainable, cost-efficient, and biocompatible, which highlight the excellent translational potential in clinical settings.

Structures and immunomodulatory activity of one galactose- and arabinose-rich polysaccharide from Sambucus adnata.

One galactose- and arabinose-rich polysaccharide isolated from Sambucus adnata was named SPS-1, which had an average molecular weight 138.52 kDa, and was composed of L-rhamnose, D-glucuronic acid, D-galacturonic acid, D-galactose, and L-arabinose in a molar ratio of 0.6:0.4:0.1:4.9:4.0. The primary structure of SPS-1 was further analyzed through methylation and NMR spectroscopy. The results showed that SPS-1 had the structural characteristics of AG-II pectin. The immunoactivity test showed that SPS-1 activated the phosphorylation of MAPKs-related proteins and further elevated the expression levels of related nuclear transcription factors (IκBα and NF-κB p65) in the cells through the TLR2 and MyD88/TRAF6-dependent pathway, thereby significantly enhancing the phagocytosis of macrophages and stimulating the secretion of NO, IL-1ß, IL-6, and TNF-α, which activated the RAW264.7 cells. Therefore, SPS-1, acting as an immunomodulator, is a potential drug for immunological diseases.

Incidence and risk factors of postoperative delirium following total knee arthroplasty: A retrospective Nationwide Inpatient Sample database study.

BACKGROUND: Postoperative delirium is a common complication following major surgeries, causing a variety of adverse effects. However, the incidence and risk factors of delirium after primary total knee arthroplasty (TKA) has not been well studied using a large-scale national database. METHODS: A retrospective database analysis was performed based on Nationwide Inpatient Sample (NIS) from 2005-2014. Patients who underwent primary TKA were included. Patient demographics, comorbidities, length of stay (LOS), total charges, type of payer, in-hospital mortality, and perioperative complications were evaluated. RESULTS: A total of 1,228,879 TKAs were obtained from the NIS database. The general incidence of delirium after TKA was 1.00%, which peaked in the year 2008.Patients with delirium after TKA presented increased comorbidities, LOS, hospital charges, usage of medicare, and in-hospital mortality (P < 0.0001). Delirium following TKA was associated with medical complications during hospitalization including acute renal failure, acute myocardial infarction, pneumonia, pulmonary embolism, stroke, and urinary tract infection. Risk factors of postoperative delirium included advanced age, neurological disorders, alcohol and drug abuse, depression, psychoses, fluid and electrolyte disorders, diabetes, weight loss, deficiency and chronic blood loss anemia, coagulopathy, congestive heart failure, chronic pulmonary disease, pulmonary circulation disorders, peripheral vascular disorders, chronic renal failure, and teaching hospital. Notably, neurological disorders were found to have the strongest association with the occurrence of postoperative delirium. CONCLUSION: A relatively low incidence of delirium after TKA was identified. It is of benefit to study risk factors of postoperative delirium to ensure the appropriate management and moderate its consequences.

Factors related to stent patency and early elimination of jaundice using bile duct stent combined with iodine-125 seed implantation in malignant obstructive jaundice.

Purpose: Biliary stents combined with percutaneous or endoscopic ultrasound-guided iodine-125 seed implantation into primary tumor have been confirmed to relieve malignant obstructive jaundice (MOJ), and prolong patient's stent patency. The aim of the study was to evaluate meaningful clinical application indications and better guide the application of this technology. Material and methods: Patients with MOJ, who have received bile duct stenting combined with iodine-125 (125I) seed implantation from October, 2010 to April, 2022, were retrospectively analyzed. Univariate and multivariate analyses were adopted to indicate factors of stent patency in MOJ and influencing factors of jaundice reduction at one week after surgery. Results: A total of 90 patients were enrolled into the study, including 52 males (57.8%) and 38 females (42.2%), with a mean age of 68.66 ±12.53 years. The median stent patency was 8 months. No serious adverse events occurred during follow-up. Multivariate analysis showed that Child-Pugh score (HR = 2.221, 95% CI: 1.081-4.562), biliary infection (HR = 1.901, 95% CI: 1.084-3.335), and pre-operative jaundice duration (HR = 1.977, 95% CI: 1.106-3.533) were the independent risk factors for stent patency. Child-Pugh B/C (OR = 4.647, 95% CI: 1.080-19.982) and bile duct infection (OR = 3.583, 95% CI: 1.095-11.725) were the independent risk factors for jaundice reduction at one week after surgery. Conclusions: MOJ patients treated with biliary stents combined with 125I seed implantation, and patients with better pre-operative liver function and no biliary tract infection, present not only longer biliary stent patency, but also better early jaundice reduction.

Impact of valvular heart disease on hip replacement: a retrospective nationwide inpatient sample database study.

BACKGROUND: To study the impact of valvular heart disease (VHD) on hip replacement, particularly the clinical impactions of aortic stenosis before total/partial hip arthroplasty. METHODS: This was a retrospective cohort study. Data on patients who had undergone hip replacement from 2005 to 2014 were extracted from the NIS database. Independent t test and chi-square test were used to analyze the essential characteristics of patients. Multivariate regression was used to estimate the correlation among demographics, comorbidities, complications, hospitalization costs, and time. RESULTS: VHD accounted for 5.56% and AS accounted for 0.03% of the patients before hip replacement surgeries. Patients with VHD before hip replacement are related to the following characteristics: female patients (odds ratio [OR] = 1.15 [1.12-1.18]), elective admission (OR = 0.78 [0.76-0.80]), Charlson Comorbidity Index ≥3 (OR = 1.06 [1.03-1.08]), large-volume hospitals (OR = 1.13 [1.1-1.2]), teaching hospitals (OR = 5 4.4 [2.9-6.7]), and hospital location in urban areas (OR = 1.22 [1.2-1.3]). In addition, VHD is a risk factor for mortality and some acute postoperative medical complications, such as acute cardiac event (OR = 2.96 [2.87-3.04]), acute pulmonary edema (OR = 1.13 [1.06-1.21]), acute cerebrovascular event (OR = 1.22 [1.16-1.74]), and acute renal failure (OR = 1.22 [1.17-1.27]). It also has an impact on DVT/PE (OR = 0.89 [0.8-0.99]). Patients with AS before hip replacement have basic demographic characteristics like those of hip replacement patients with valvular disease. Patients with AS are older than those without AS before surgery (OR = 3.28 [2.27-4.75) and are related to the following characteristics: female patients (OR = 1.92 [1.32-2.8]) and elective admission (OR = 0.51 [0.36-0.75]). The perioperative period is limited to acute postoperative complications, such as acute cardiac events (OR = 2.50 [1.76-3.53]) and acute hepatic failure (OR = 7.69 [1.8-32.89]). Both valvular diseases and AS are associated with a higher mortality rate and hospitalization cost. CONCLUSION: VHD independently predicted mortality rate and surgical and medical complications after total/partial hip arthroplasty.

Nanohydroxyapatite, Nanosilicate-Reinforced Injectable, and Biomimetic Gelatin-Methacryloyl Hydrogel for Bone Tissue Engineering.

PURPOSE: Given that autologous bone graft for bone defects is limited by insufficient supply and morbidity at the donor site, developing biomimetic graft materials as an alternative has gained consistent attention. However, obstacles in designing bone-mimetic materials that could integrate the biomimetic nature of the bone extracellular matrix, osteogenic cells, and osteoinductive ingredients with a fast and convenient strategy still exist. METHODS: This study designed and fabricated a mesenchymal stem cell (MSC)-laden, nanohydroxyapatite (HAP), and nanosilicate (SN)-loaded bone mimetic and injectable gelatin-methacryloyl hydrogel (GelMA-HAP-SN) system for bone tissue engineering, and systemically investigated the osteogenic capacity of GelMA-HAP-SN in vitro and in vivo. RESULTS: Introducing HAP enhanced the compositional similarity to the natural bone extracellular matrix, and SN loading endowed the hydrogel with injectable and osteogenic ability. As a result, the GelMA-HAP-SN hydrogel demonstrated an increase in cellular viability, proliferation, and spreading behavior. The GelMA-HAP-SN hydrogel also amplified the embedded MSCs' osteogenic biomarkers' expression and matrix mineralization. Furthermore, the MSC-encapsulated GelMA-HAP-SN hydrogel was injected into rats' critical-sized calvaria defect, and micro-CT and histomorphometry staining results further confirmed its excellent bone regeneration ability. CONCLUSION: These MSC-loaded GelMA-HAP-SN hydrogels are potential graft materials for bone defect treatment.

The Protective Effects of Parathyroid Hormone (1-34) on Cartilage and Subchondral Bone Through Down-Regulating JAK2/STAT3 and WNT5A/ROR2 in a Collagenase-Induced Osteoarthritis Mouse Model.

OBJECTIVE: To assess the effects of PTH (1-34) on bone and cartilage metabolism in a collagenase-induced mouse model of osteoarthritis (OA) and examine whether PTH (1-34) affects the expression of JAK2/STAT3 and WNT5A/ROR2 in this process. METHODS: Eighteen 12-week-old male C57Bl/6 mice were randomly assigned into three groups as follows: sham group (Group A), the collagenase + saline injection group (Group B), and the collagenase + PTH (1-34) treatment group (Group C). Collagenase was injected (intra-articular) into the knee joint of Group B and C. The PTH (1-34)-treatment was started at 6 weeks after the operation and lasted for 6 weeks. Cartilage pathology was evaluated by gross visual, histological, and immunohistochemical assessments. Subchondral bone was evaluated by microcomputed tomography (micro-CT) and immunohistochemical analyses. RESULTS: The OARSI macroscopic and microscopic scores of Group B were higher than those of Group A (P = 0.026; P = 0.002, respectively). Group C showed statistically significant differences in macroscopic and microscopic scores from Group B (P = 0.041; P = 0.008, respectively). The results showed that the Col-II and AGG expression levels in the cartilage tissue were significantly lower in Group B than Group A (P < 0.001; P = 0.008, respectively). The Col-II and AGG expression levels were significantly higher in Group C than Group B (P = 0.009; P = 0.014, respectively). MMP-13, ADAMTS-4, Caspase-3, P53, and Bax expression levels were significantly higher in Group B than the Group A (P < 0.001; P < 0.001; P = 0.04; P < 0.001; P = 0.005, respectively); however, the cartilage tissue in Group C showed significantly less ADAMTS-4, MMP-13, Caspase-3, P53, and Bax expression than Group B (P < 0.001, P < 0.001, P = 0.044; P = 0.002; P = 0.005, respectively). Over-expressed JAK2/STAT3 and WNT5A/ROR2 were observed in both cartilage and subchondral bone in this model; however, these changes were prevented by PTH (1-34) treatment. These parameters (bone mineral density, bone volume ratio, trabecular bone pattern factor, and structure model index) of micro-CT indicated subchondral bone loss and architecture changes in Group B, but improvements in these parameters in Group C. CONCLUSIONS: PTH (1-34) exhibits protective effects on both cartilage and subchondral bone in a collagenase-induced OA mouse model, and it may be involved in down-regulating the expression of JAK2/STAT3 and WNT5A/ROR2.